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Electron microscopy reveals details of HIV gut infection

A team of researchers used high-resolution electron microscopy to provide the most detailed characterization yet of HIV infection in the gut, according to a recent study published in PLOS Pathogens.

The researchers at the California Institute of Technology were the first to use high-resolution electron microscopy to look at HIV infection within the tissue of an infected organism. Learning more about how HIV infects the gut, which is one of the first parts of the body attacked during infection, could help researchers to develop new therapies against the deadly virus.

"Looking at a real infection within real tissue is a big advance," Mark Ladinsky, the lead author of the paper, said. "With something like HIV, it's usually very difficult and dangerous to do because the virus is an infectious agent. We used an animal model implanted with human tissue so we can study the actual virus under, essentially, its normal circumstances."

The researchers used electron tomography to take three-dimensional images of normal cells along with HIV-infected tissues from the gut of a mouse model engineered to express a human immune system. Pamela Bjorkman, a researcher on the project, said the study was the first to use the technology to look at HIV interacting with other cells in real gut tissue.

Ladinsky and Bjorkman used the detailed images to confirm multiple observations of HIV made in prior, in vitro studies, including the behavior and structure of the virus when it buds off of infected cells. The team also found multiple novel observations.

"The study suggests that an infected cell releases newly formed viruses in a semi-synchronous wave pattern," Ladinsky said. "It doesn't look like one virus buds off and then another in a random way. Rather, it appears that groups of virus bud off from a given cell within a certain time frame and then, a little while later, another group does the same, and then another, and so on."

The researchers also found that HIV can transfer via free pools of free virus, which could mean that treatment with protein-based drugs like antibodies could augment or replace treatment regimens using small-molecule antiretroviral drugs.

"The end goal is to look at a native infection in human tissue to get a real picture of how it's working inside the body, and hopefully make a positive difference in fighting this epidemic," Bjorkman said.